Steroid intermediates



States Patent "Ce M82384 Patented Apr. 14, 1959 EXAMPLE I Reaction with phasgenv 2882284 A solution of one gram of 2' 1-hydroxy-pregnane=3;2tt STERDID INIERMEDIATES 5 citing; nlet lfaengene vrz'las fadiei dropvivisg tola: s r uiono a o o enen-m'i ni i g gfig ajif gf' ag ggfg ggi 3135 zene containing onem lt of py idin Thesolution: was

stirred two hours at 25 C. and evaporated to dryness inmm of Delaware I vacuo. The residue was 21-hydroxy-pregnane-3,20-dione No Drawing. Application January 11, 1955 10 chloroformate. The equation for this reaction is as Serial No. follows:

6 Claims. (01. zoo-397.47) cm g ns...

This invention is concerned with certain novel steroidcompounds which are useful as intermediates. Thisiapplication is a continuation-in-part of application Serial Number 474,977, filed December 13, 1954, by Gerald D. Laubach, and now abandoned. That application was a continuation-in-part of parent application Serial Number 463,805, filed October 21, 1954, and now abandoned. Another continuation-in-part of this parent application j g g was filed on January 7, 1955, and has issued as US.

CH3 CH: V

E CHM E X so EXAMPLEII Patent 2,708,651. In this last mentioned application, there Reaction with p-chlomethyl chloroformate is described the use of these compounds as intermediates for the synthesis of central nervous system depressants.

These compounds are those having. the formula 0 One half gram of p-chloroethyl chloroformate was added to a stirred; cooled solution of one gram of 21- hydroxy-pregnane-3,ZO-dione in 5 ml. of pyridine and the solution allowed to stand 24 hours. It was then stirred into 20 ml. of ice cold 3 N sulfuric acid and extracted in which X is chosen from the group consisting of Cl, three times with 15 ml. of chloroform. After washing c c with 1 N sulfuric acid, water and sodium bicarbonate CH -Cl, and CH CH -COOH. This generic forsolution, the chl'oroformextract wasdriedover anhydrous mula includes both compounds of the pregnane series, that sodium sulfate and evaporated todryness in vacuo. Tritis, compounds having the formula uration of the residue with ether yielded the crystalline 21-hydroxy pregnane-3;20-dione fl-chloroethyl carbonate. The equation for this reaction is asfollows:

CH3 CH3 Ol-G-O-CHr-CHiGl H o and also compounds of the allopregnane series, that is, H compounds having the formula 0H1". -01 H CH3 A-o-om-o-c-x 1; 1 so 3- 0 I v '5 H v I H: The compounds of this invention are prepared by re- 0H 0:0 actions at the 21-position hydroxyl group of either 21- hydroxy pregnane 3,20 dione, or 21 hydroxyallopregnane-3,20-dione. The reagents used are phosgene,

,B chloroethyl chloroformate, 18 chloroethylisocyanate, chloroacetyl chloride and succinic anhydride. The following examples illustrate the use of each of these reagents.

a w 3: z If n" 82,284 l v, I. a. y K i t V 3 I; v t I I. i 4

EKAMPLE III pyridine was neutralized with 3 N hydrochloric acid and 'R A- with fichlomethyfisoyanme the solution further diluted with 2 l. of ice water. The

precipitated product was filtered, washed with water and 0115 gram of y i y'p was dried in vacuo at 50 C. The product was identified as solved in 5 ml. Of dlmCthYlfOl'fllfiMidB and treated with 5 21-hyd1'oxy-pregnane-3 ,20-dione-hemi5ucinate 0.6 gram of fl-chloroethylisocyanate' After standing 18 hours, the mixture was poured into water and the pre- EXAMPLE cipitated product filtered off and washed with water. preparation of allo compounds The product was 21-hydroxy-pregnane-3,ZO-dione fl-chloroethylcarbamate. The equation for this reaction is as Examples 1 to 5 mcluswe were repeated with no .change fuwS: except the use of 21-hydroxya1lopregnane-3,20-d1one in v place of 2l-hydroxy-pregnane-3,ZO-dione. In each case, OH; 3, the reaction proceeded in identical fashion and the correg T spending allo compound was obtained.

' The foregoing examples are given solely for the purpose of illustration, and are not to be considered as limita- 1 tions of this invention, many variations of which are n pgssible without departing from the spirit or scope there- 0 o p :What is claimed is:

- '1. A-compound having the formula CH: CH

j mm

wherein'X-is chosen from the group consisting of Cl,

2. A compound having the formula H C o-om-o-o-cn EXAMPLEIV v Reaction with chloroacetyl chloride 1 a 0 To a solution of 21-hydroxy-pregnane-3,ZO-dione in 'pyridinewas added two molar equivalents ofjchloroacetyl chloride. After 12 hours, the product; 21-hydro ty- A compoupd havmg the formula pregnane-3,20-dione chloroacetat'e', was isolated by precm OH; I cipitation with a large volume of dilute, acidified ice I OH O CI O OHF'OHPG1 water. The equation for this reaction is as follows: i) i) H a i i t C c-cmon 5s i ClC-CH:C1 4. A compound having the formula 0 t CH 9 1 C-CHrO-C-NH-CHr-CHz-Cl jE-CIb-O-E-CECI 6o g o 5. A compound having the formula EXAMPLE v OH; o-cm-o-o-wm-ot i Reaction with succinic anhydride i j g g A solution of-14 grams of 2l-hydroxy-pregnane-3,20- dione and 01314 grams of recrystallized succinic anhydride in ml. of dry pyridine was allowed to stand at room 6- temperaturejox; l8hburs, then cooled in an ice bath and poured in a fine" stream into 1.5 l. of ice water. Excess 1 g;

5 6 6. A compound having the formula References Cited in the file of this patent CH8 CH3 CH 000E UNITED STATES PATENTS g g P 2,183,589 Reichstein Dec. 19, 1939 5 2,312,483 Reichstein Mar. 2, 1943 2,708,651 Laubach May 17, 1955 

1. A COMPOUND HAVING THE FORMULA 